Resistance of murine LTA cells to oncogene--mediated progression from tumorigenic to metastatic phenotype.
We have previously shown that expression of the H-ras oncogene alone does not induce progression of a tumorigenic but non-metastatic murine fibroblast cell line (LTA) to a metastatic phenotype. Because myc genes, alone or with ras, have been implicated at different stages of progression in other systems, we examined the ability of v-myc, alone and in combination with H-ras, to induce malignant conversion of LTA. We found no increase in either "spontaneous" (assessed after s.c. injection into nude mice) or "experimental" (assessed after i.v. injection into chick embryos) metastatic ability in spite of high levels of v-myc RNA in LTA cells transfected with v-myc alone. Serial in vivo passaging did not consistently select for either myc expression or metastatic ability. Myc transfected cells expressing high levels of myc RNA were subsequently transfected with H-ras. LTA cells expressing both oncogenes at high levels remained non-metastatic. LTA cells thus are resistant to the effects of myc and ras oncogenes (alone and in combination) on a specific stage of tumor progression, that of malignant conversion, and may offer a good model for studying mechanisms of resistance to these oncogenes.
Tuck
A B
AB
London Regional Cancer Centre, Ontario, Canada.
Wilson
S M
SM
Chambers
A F
AF
D000818:Animals; D015152:Blotting, Northern; D015139:Blotting, Southern; D002460:Cell Line; D002471:Cell Transformation, Neoplastic; D002642:Chick Embryo; D004273:DNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D005347:Fibroblasts; D016259:Genes, myc; D011905:Genes, ras; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D010641:Phenotype; D012334:RNA, Neoplasm / Q000235:genetics / Q000302:isolation & purification; D014162:Transfection
D004273:DNA, Neoplasm; D012334:RNA, Neoplasm